MODELS OF HEREDITY RETINAL DEGENERATION

遗传性视网膜变性模型

• 批准号: 6624960
• 负责人: GREGORY M ACLAND
• 金额: $ 66.02万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6624960
• 关键词: animal breeding; animal colony; apoptosis; cell transplantation; cooperative study; disease /disorder model; dogs; gene mutation; gene therapy; genetic models; genetic strain; inborn biological transport disorder; model design /development; molecular cloning; nonhuman therapy evaluation; retina degeneration; retinal pigment epithelium; transfection; visual photoreceptor

DESCRIPTION: (Applicant's Abstract) This application's purpose is to make available to the research community certain canine strains affected with hereditary retinal degenerations, in order to facilitate research into the causes and cures of such diseases in people. This resource project, continuously managed by the principal investigators for the past 20 years, has 3 broad aspects. The first is to serve as a center for production and distribution, primarily to other independent research investigators, of 5 canine mutant models of hereditary retinal degenerations affecting humans. The need for these animals in research is addressed, as is the importance of maintaining them in a centralized breeding and distribution facility. The second objective is to continue collaborative studies already established to clone the genes for these diseases, investigate the cellular and molecular biology of these diseases, and develop methods for therapeutic intervention. The third aspect is to make available the physical and personnel resources supported by this project for instituting and conducting therapeutic trials as initiated by independent research investigators, either from academic or industrial organizations. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Five strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcdl, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd, and the newly available RPE65 mutant dog strain), together with appropriate nonaffected control dogs, will be bred and maintained. The progeny of these dogs will be distributed to research investigators, either directly or by collection, processing and distribution of requested tissues. Utilization of these mutants will be promoted by solicitation of requests from investigators. Assistance will be offered to investigators in development and implementation of specific protocols for optimal utilization of these mutants. Specific collaborative research includes programs to: identify, clone, and characterize the gene in cd, erd, prcd, and rcdl; cd, erd and prcd; determine and compare the role of programmed cell death genes in cd, erd, prcd, and rcdl; define the cause of abnormalities in docosaehexanoic acid transport & metabolism in prcd and identify candidate genes responsible for these deficiencies; further develop therapies for hereditary retinal degenerations including vector mediated gene transfer into canine photoreceptors; photoreceptor and retinal pigment epithelial cell transplantation into canine retina; and application of a visual-prosthetic silicon chip retinal implant.

描述：(申请人摘要)本申请的目的是为了 向研究界提供某些受影响的犬种 遗传性视网膜退行性变，以促进对 人类患此类疾病的原因和治疗方法。这个资源项目， 在过去的20年里，由主要调查人员持续管理， 三个大的方面。一是以生产为中心， 分发，主要分发给其他独立研究调查人员，5 影响人类的遗传性视网膜变性的犬种突变模型。这个 在研究中对这些动物的需求得到了解决，同时也说明了 将它们保存在集中的繁殖和分发设施中。这个 第二个目标是继续已经建立的合作研究，以 克隆这些疾病的基因，研究细胞和分子 这些疾病的生物学，并开发治疗干预的方法。 第三个方面是物力和人力资源 由该项目支持，用于建立和进行治疗试验， 由独立研究人员发起，来自学术界或 产业组织。每项这样的协作研究都经过同行评审， 另外，作为合作调查人员研究协议的一部分。 五个品系的狗，每个品系传递一种不同的基因，以表现良好的特征 遗传性视网膜变性(视锥细胞发育不良1型，进行性 视杆-视锥细胞变性、视网膜早期变性、视锥细胞变性 CD和新获得的RPE65突变犬品系)，以及适当的 不受影响的对照犬，将被饲养和维护。这些人的后代 狗将被直接或通过以下方式分发给研究人员 收集、加工和分发所要求的组织。利用 这些突变体将通过征求调查人员的请求而得到推广。 将在开发和实施方面向调查人员提供援助 最大限度地利用这些突变体的特定方案。 具体的协作研究包括以下计划：识别、克隆和 鉴定cd、erd、prcd和rcdl；cd、erd和prcd中的基因；确定 比较程序性细胞死亡基因在CD、ERD、PRCD和RCD1中的作用； 确定二十二碳己酸转运异常的原因 PRCD中的新陈代谢并确定与此相关的候选基因 缺乏；进一步开发遗传性视网膜变性的治疗方法 包括载体介导的犬光感受器基因转移； 光感受器和视网膜色素上皮细胞移植入犬体内 视网膜；以及视觉假体硅芯片视网膜植入物的应用。